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June 5, 1996

Making New Drugs via Combinatorial Chemistry

Author Affiliations

JAMA contributor

JAMA. 1996;275(21):1624-1626. doi:10.1001/jama.1996.03530450014006

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DRUG DEVELOPMENT, as a problemsolving enterprise, uses a combination of two different approaches—one deductive, the other inductive. The deductive approach is characterized by a shotgun approach of testing a host of compounds thought to have specific pharmacologic properties to see which have the greatest effect on the test subject. The process moves from generalized knowledge to specific application and has always been time-consuming and labor-intensive.

The inductive approach, which is considered more intellectually challenging, starts with a structural understanding of a drug's binding site to more narrowly search for, or design and synthesize, its specific complement. This structure-based design approach moves from specific information to more generalized application.

Structure-based design has made substantial strides in the past decade. Six months ago, for example, Jane E. Brody in the New York Times (November 7, 1995) described the work of a Cornell University research team that received a $3.3 million grant from